Deficiency of the
membrane protein FAT/CD36 causes a marked defect in
fatty acid uptake by various tissues and is genetically linked to
insulin resistance in rats and humans. Here, we examined
insulin responsiveness of CD36-/- mice. When fed a diet high in complex
carbohydrates and low (5%) in fat, these animals cleared
glucose faster than the wild-type. In vivo, uptake of 2-fluorodeoxyglucose by muscle was increased severalfold, and in vitro,
insulin responsiveness of glycogenesis by the soleus was enhanced. Null mice had lower
glycogen levels in muscle and liver, lower muscle
triglyceride levels, and increased liver
triglyceride content--all findings consistent with increased
insulin-sensitivity. However, when the chow diet was switched to one high in
fructose, CD36-/- mice but not wild-type mice developed marked
glucose intolerance,
hyperinsulinemia, and decreased muscle
glucose uptake. High-fat diets
impaired glucose tolerance equally in both groups, although
CD36 deficiency helped moderate
insulin-responsive muscle
glucose oxidation. In conclusion,
CD36 deficiency enhances
insulin responsiveness on a high-
starch,
low-fat diet. It predisposes to
insulin resistance induced by high
fructose and partially protects from that induced by high-fat diets. In humans,
CD36 deficiency may be an important factor in the metabolic adaptation to diet and in susceptibility to some forms of diet-induced pathology.